Jin Meilan, Takahashi Miwa, Moto Mitsuyoshi, Muguruma Masako, Ito Kazumi, Watanabe Kyoko, Kenmochi Yusuke, Kono Taichi, Hasumi Keiji, Mitsumori Kunitoshi
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan.
Arch Toxicol. 2007 Dec;81(12):883-94. doi: 10.1007/s00204-007-0218-1. Epub 2007 Jun 14.
To evaluate the carcinogenicity of troglitazone in rasH2 mice, 7-week-old male and female rasH2 mice were fed a diet containing 0, 3,000 or 6,000 ppm troglitazone for 26 weeks. An increased tendency in the incidence of vascular tumors was observed in females of the 6,000 ppm group. The preliminary analysis using a high-density oligonucleotide microarray on a splenic hemangiosarcoma of a high dose female that could be obtained as a fresh sample showed that several genes related to the ras/MAPK pathway activation, angiogenesis, cell cycle and cell multiplication were up-regulated. In addition, most of the genes up-regulated were confirmed by the reverse transcriptase-polymerase chain reaction (RT-PCR). These results may suggest that the carcinogenic susceptibility of rasH2 mice to troglitazone is relatively low and up-regulations of the ras/MAPK pathway and angiogenesis-related genes are probably involved in the production of splenic hemangiosarcomas in rasH2 mice given troglitazone.
为评估曲格列酮对rasH2小鼠的致癌性，给7周龄的雄性和雌性rasH2小鼠喂食含0、3000或6000 ppm曲格列酮的饲料，持续26周。在6000 ppm组的雌性小鼠中观察到血管肿瘤发生率有增加趋势。对一只高剂量雌性小鼠脾脏血管肉瘤新鲜样本进行高密度寡核苷酸微阵列初步分析，结果显示与ras/MAPK通路激活、血管生成、细胞周期和细胞增殖相关的几个基因上调。此外，通过逆转录聚合酶链反应（RT-PCR）证实了大多数上调基因。这些结果可能表明，rasH2小鼠对曲格列酮的致癌易感性相对较低，ras/MAPK通路和血管生成相关基因的上调可能与给曲格列酮的rasH2小鼠脾脏血管肉瘤的发生有关。
